A combination of behavioral, physiological, and pharmacological approaches was used to study the neural mechanisms involved in pain and analgesia. To address the mechanisms of dorsal horn plasticity and hyperalgesia following inflammation, a neurotoxin, capsaicin, was used to selectively destroy a subpopulation of small diameter primary afferents. The effects of adjuvant-induced inflammation on dorsal horn neuronal activity and nociception were studied in the neonatal capsaicin-treated rats. Capsaicin treatment resulted in an over 85% loss of unmyelinated fibers in L5 dorsal roots. The thermal nociceptive threshold was increased in capsaicin-treated rats, but behavioral hyperalgesia still developed. There was a significant decrease in the percentage of dorsal horn nociceptive neurons that responded to C-fiber stimulation and noxious heating of the skin. The expansion of receptive fields, a hallmark of the effect of inflammation-induced plasticity, was less extensive for nociceptive specific (NS), but not for wide dynamic range (WDR), neurons. Compared to vehicle-treated rats, a smaller population of NS neurons had background activity. An NMDA receptor antagonist, MK-801, reduced the receptive field size of dorsal horn neurons and attenuated the behavioral hyperalgesia in capsaicin-treated rats. These results indicate a complex effect of neonatal capsaicin treatment in rat model of inflammation/hyperalgesia. The data suggest that unmyelinated and fine myelinated primary afferents play important roles in triggering dorsal horn plasticity. Additionally, NMDA receptors appear to function at least in part independent of small diameter primary afferent axons.